Hepatic glucose output is regulated by intrinsic and hormonal factors. The ratio of insulin to glucagon (I/G) concentration in the plasma has been shown to influence glucose output. To further explore the importance of the I/G ratio on glucose output experiments will be carried out using 3 agents which were found to increase glucose output in the normal dog but have different effects on plasma glucose levels. Phloridzin infusion causes a prompt glucosuria without a significant fall in glucose concentration in the hepatic artery or portal vein. Clonidine infusion results in a gradual rise in plasma glucose levels which begins only after a 15-30 minute lag period. Isoproterinol infusion causes a prompt but brief hyperglycemia. The studies will be performed in conscious normal dogs, using an infusion of 6-3H-glucose to measure rates of hepatic glucose production and uptake by tissues.